Gallbladder cancer: Progress in the Indian subcontinent.

Gallbladder cancer (GBC) is one of the commonest biliary malignancies seen in India, Argentina, and Japan. The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs. Early detection is the only way to improve the outcome. There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC. Therefore, it is important and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis, early diagnosis, treatment, and prognostication. As India being one of the largest hubs for GBC in the world, it is important to know how the country has progressed on GBC. In this review, we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.

Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases. / ç£·é ¸äºŒé ¯é ¶4æŠ‘åˆ¶å‰‚åœ¨ä¸­æž¢ç¥žç»ç³»ç»Ÿç–¾ç— ä¸­çš„ä½œç”¨ç ”ç©¶è¿›å±•.

Phosphodiesterase (PDE) hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and involve in the regulation of cellular physiological processes and neurological functions, including neuronal plasticity, synaptogenesis, synaptic transmission, memory formation and cognitive function by catalyzing the hydrolysis of intracellular cAMP and cGMP. A large number of basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system (CNS) diseases by inhibiting cAMP hydrolysis, increasing cAMP content and enhancing its downstream effects. PDE4 inhibitors have long-term potentiation effect, which can enhance phosphorylation of cAMP response element binding protein (CREB) and upregulate expression of memory related Arc genes in hippocampal neurons, thereby improving cognitive impairment and Alzheimer's disease-like symptoms; and also resist the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by α-syn and increasing the effect of miR-124-3p on cell activity. Alteration of PDE4 activity is the molecular basis of psychosis and cognitive disorders, therefore it is considered as one of the therapeutic targets for schizophrenia. PDE4 inhibitors play a role in depression; Autism spectrum and Huntington's disease by inhibiting the advanced glycation end product receptor (RAGE), TLR4 and NLRP3 pathways in the hippocampus, reducing the activation of microglia and the production of interleukin-1ß, down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors and Increase the nociception threshold. PDE4 inhibitors might be used in treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein (FMRP). PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination, which has potential in the treatment of multiple sclerosis. PDE4 also related to Bipolar disorder which may be one of the therapeutic targets. At present, several PDE4 inhibitors are on clinical trials for treatment of CNS diseases. This article reviews and discusses the progress on basic researches and clinical trials of PDE4 inhibitors in CNS diseases, providing reference for the prevention and treatment of CNS diseases and the development of new drugs.

Frontiers and future perspectives of neuroimmunology.

Neuroimmunology is an interdisciplinary branch of biomedical science that emerges from the intersection of studies on the nervous system and the immune system. The complex interplay between the two systems has long been recognized. Research efforts directed at the underlying functional interface and associated pathophysiology, however, have garnered attention only in recent decades. In this narrative review, we highlight significant advances in research on neuroimmune interplay and modulation. A particular focus is on early- and middle-career neuroimmunologists in China and their achievements in frontier areas of "neuroimmune interface", "neuro-endocrine-immune network and modulation", "neuroimmune interactions in diseases", "meningeal lymphatic and glymphatic systems in health and disease", and "tools and methodologies in neuroimmunology research". Key scientific questions and future directions for potential breakthroughs in neuroimmunology research are proposed.

Application of emerging technologies in ischemic stroke: from clinical study to basic research.

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke.

Research Progress of Baihe Gujin Decoction in the Treatment of Lung Cancer.

Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and ß-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America.

Objective: Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods: Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results: A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions: In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

Review of the Development of Meniscus Centralization.

PURPOSE OF REVIEW: With an aging population, extending healthy life expectancy is a global challenge. Maintaining healthy knee joint function is one of the essential factors to preserve the ability to walk and extend healthy life expectancy. Meniscus centralization was introduced in 2012 as a procedure for meniscus extrusion, one of the causes of knee osteoarthritis (OA). Initially, it was performed only for lateral meniscus (LM) extrusion, and favorable 2-year results were reported in 2016. Gradually, basic studies supporting the effectiveness of meniscus centralization have been reported, and it has also been performed for medial meniscus (MM) extrusion, with some positive results reported. Although the surgical procedures vary among the institutions, the basic concept is to reattach the loosened meniscotibial ligament to the edge of the tibial plateau to re-tension it. This review will discuss the history of development and the current status of meniscus centralization. RECENT FINDINGS: Current research shows that meniscus centralization is not performed in isolation but is often used as an augmentation along with the conventional repair of meniscus injuries, particularly posterior root tears. Biomechanical studies demonstrated that MM centralization with a posteromedial anchor can better restore meniscus function. CONCLUSION: Despite its relatively short publication history of just over ten years, meniscus centralization has shown potential as a treatment to curb the progression of knee OA and extend a healthy life. While more evidence is needed, this conclusion underscores the promising role for meniscus centralization, making it a topic of significant interest for knee surgeons and researchers.

Alzheimer's disease-related presenilins are key to intestinal epithelial cell function and gut immune homoeostasis.

OBJECTIVE: Mutations in presenilin genes are the major cause of Alzheimer's disease. However, little is known about their expression and function in the gut. In this study, we identify the presenilins Psen1 and Psen2 as key molecules that maintain intestinal homoeostasis. DESIGN: Human inflammatory bowel disease (IBD) and control samples were analysed for Psen1 expression. Newly generated intestinal epithelium-specific Psen1-deficient, Psen2-deficient and inducible Psen1/Psen2 double-deficient mice were used to dissect the functional role of presenilins in intestinal homoeostasis. RESULTS: Psen1 expression was regulated in experimental gut inflammation and in patients with IBD. Induced deletion of Psen1 and Psen2 in mice caused rapid weight loss and spontaneous development of intestinal inflammation. Mice exhibited epithelial barrier disruption with bacterial translocation and deregulation of key pathways for nutrient uptake. Wasting disease was independent of gut inflammation and dysbiosis, as depletion of microbiota rescued Psen-deficient animals from spontaneous colitis development but not from weight loss. On a molecular level, intestinal epithelial cells lacking Psen showed impaired Notch signalling and dysregulated epithelial differentiation. CONCLUSION: Overall, our study provides evidence that Psen1 and Psen2 are important guardians of intestinal homoeostasis and future targets for barrier-promoting therapeutic strategies in IBD.

Vulnerabilities in social anxiety: Integrating intra- and interpersonal perspectives.

What are the major vulnerabilities in people with social anxiety? What are the most promising directions for translational research pertaining to this condition? The present paper provides an integrative summary of basic and applied translational research on social anxiety, emphasizing vulnerability factors. It is divided into two subsections: intrapersonal and interpersonal. The intrapersonal section synthesizes research relating to (a) self-representations and self-referential processes; (b) emotions and their regulation; and (c) cognitive biases: attention, interpretation and judgment, and memory. The interpersonal section summarizes findings regarding the systems of (a) approach and avoidance, (b) affiliation and social rank, and their implications for interpersonal impairments. Our review suggests that the science of social anxiety and, more generally, psychopathology may be advanced by examining processes and their underlying content within broad psychological systems. Increased interaction between basic and applied researchers to diversify and elaborate different perspectives on social anxiety is necessary for progress.

Interleukin-18 Binding Protein (IL-18BP): A Long Journey From Discovery to Clinical Application.

IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rß chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.

The Sixth Brainstorming Research Assembly for Young Neuroscientists (BraYn), Naples, Italy, 27-29 September 2023.

The BraYn association aims to bolster young neuroscientists' research endeavors through collaborative support, fundraising assistance, and events promoting knowledge exchange and collaboration across Europe. Central to its mission is the annual BraYn conference, tailored for PhD students, postdocs, junior PIs, neurologists, and clinicians. This gathering champions cooperation, offering talks by key figures, educational workshops, and opportunities for attendees to present their work, compete for grants, and engage in international scientific experiences. The conference, established in 2018, has grown substantially in attendance and industry support and was adapted during the pandemic with virtual editions. The last sixth edition in Naples (27-29 September 2023) attracted over 300 delegates, focusing on peer-to-peer discussions, interdisciplinary collaboration, and interaction with renowned speakers, solidifying its place as a flagship event for Europe's budding neuroscience researchers.

Radiological Density, Atomic Numbers, and Stone Fragmentation of Bego Stones Used for Research in Endourology: Comparison to Real Urinary Stones.

Objective: The aim of the study was to characterize artificial stones used for research in endourology in terms of radiological properties and hardness, based on stone fragmentation, and to compare them with real stones. Materials and Methods: We built artificial stones using BegoStone Plus™ powder (BEGO, Lincoln, RI), with powder (g)-water (mL) ratios ranging from 15:03 to 15:12. The CT Gemstone Spectral Imaging Software® (GE Medical Systems, LLC, Waukesha, WI) was used to evaluate the radiological density in HU and spectral properties. Stone fragmentation was assessed in an in vitro experimental setting. These properties of artificial stones were compared with real urinary calculi. Results: Regarding radiological density in terms of HUs, 15:03 artificial calculi showed similar results when compared with real stones comprising calcium oxalate and calcium phosphate. The 15:03 and 15:04 artificial stones showed similar spectral property results to calcium pyrophosphate stones. The 15:11 artificial stones showed similar stone fragmentation results to real stones comprising uric acid, and 15:03 artificial calculi showed similar results to apatite and cystine stones. Conclusions: Artificial stones are useful for research in endourology. Stones with a powder (g)-water (mL) ratio of 15:03 proved to mimic real hard stones in terms of HUs, atomic number, and stone fragmentation in our study and could be used as artificial hard stones, and 15:11 stones showed similar stone fragmentation to uric acid stones. Our study might suggest that standard Bego stones are useful to investigate different areas in endourology, but not radiological properties because radiological homogeneity is not ensured unless more sophisticated mixing methods are used.

Gut virome in inflammatory bowel disease and beyond.

OBJECTIVE: The gut virome is a dense community of viruses inhabiting the gastrointestinal tract and an integral part of the microbiota. The virome coexists with the other components of the microbiota and with the host in a dynamic equilibrium, serving as a key contributor to the maintenance of intestinal homeostasis and functions. However, this equilibrium can be interrupted in certain pathological states, including inflammatory bowel disease, causing dysbiosis that may participate in disease pathogenesis. Nevertheless, whether virome dysbiosis is a causal or bystander event requires further clarification. DESIGN: This review seeks to summarise the latest advancements in the study of the gut virome, highlighting its cross-talk with the mucosal microenvironment. It explores how cutting-edge technologies may build upon current knowledge to advance research in this field. An overview of virome transplantation in diseased gastrointestinal tracts is provided along with insights into the development of innovative virome-based therapeutics to improve clinical management. RESULTS: Gut virome dysbiosis, primarily driven by the expansion of Caudovirales, has been shown to impact intestinal immunity and barrier functions, influencing overall intestinal homeostasis. Although emerging innovative technologies still need further implementation, they display the unprecedented potential to better characterise virome composition and delineate its role in intestinal diseases. CONCLUSIONS: The field of gut virome is progressively expanding, thanks to the advancements of sequencing technologies and bioinformatic pipelines. These have contributed to a better understanding of how virome dysbiosis is linked to intestinal disease pathogenesis and how the modulation of virome composition may help the clinical intervention to ameliorate gut disease management.

A Sustainable Translational Sheep Model for Planned Cesarean Delivery of Contraction-Free Ewes.

We evaluated whether the sheep constitutes a useful translational model to evaluate anatomical and surgical aspects of cesarean delivery (CD) from a human medical perspective with the aim of both maternal and neonatal well-being. Our hypothesis was that CD in contraction-free ewes is not associated with major complications. Primary endpoint was the transferability of anatomical conditions and surgical techniques of CD from the ewe to the human. Secondary endpoints were maternal and fetal survival, occurrence of retained fetal membranes, metritis, mastitis, or wound infections. Forty-eight Merino ewes were delivered by CD after 95% gestation (142-144 days). Both ewes and newborn lambs were cared for intensively after the delivery. Ovine uterine anatomy during CD appeared slightly different but comparable to the human uterus. Uterine incisions were mostly performed in the uterine horns, not in the uterine corpus. The ovine uterine wall is thinner than in humans. All ewes survived without any major complications. Seventy-seven (88.5%) out of 87 live-born lambs survived without any complications. The contraction-free ewe constitutes an appropriate and safe model to evaluate anatomical and surgical aspects of CD from a human medical perspective. We present a step-by-step manual for successfully planned cesarean delivery for sheep including the perioperative management illustrated with photographs and a five-minute video. With adequate planning and a reasonable number of staff, it is possible to safeguard both maternal and neonatal survival. This sustainable translational medicine model offers additional potential for the offspring to be used for further research studies (e.g., transgenerational inheritance research).

Challenges and opportunities in rare cancer research in China.

Cancer is one of the major public health challenges in China. Rare cancers collectively account for a considerable proportion of all malignancies. The lack of awareness of rare cancers among healthcare professionals and the general public, the typically complex and delayed diagnosis, and limited access to clinical trials are key challenges. Recent years have witnessed an increase in funding for research related to rare cancers in China. In this review, we provide a comprehensive overview of rare cancers and summarize the status of research on rare cancers in China and overseas, including the trends of funding and publications. We also highlight the challenges and perspectives regarding rare cancers in China.

Disruption of CerS6-mediated sphingolipid metabolism by FTO deficiency aggravates ulcerative colitis.

BACKGROUND AND AIMS: Deregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the m6A demethylases, in patients with ulcerative colitis (UC). METHODS: We analysed colon tissues of Ftoflox/flox; Villin-cre mice and their Ftoflox/flox littermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing. RNA and methylated RNA immunoprecipitation sequencing were used to analyse immunocytes and IECs. Macrophages were treated with conditioned medium of FTO-knockdown MODE-K cells or sphingosine-1-phosphate (S1P) and analysed for gene expression. Liquid chromatograph mass spectrometry identified C16-ceramide. RESULTS: FTO downregulation was identified in our in-house cohort and external cohorts of UC patients. Dysbiosis of gut microbiota, increased infiltration of proinflammatory macrophages, and enhanced differentiation of Th17 cells were observed in Ftoflox/flox;Villin-cre mice under DSS treatment. FTO deficiency resulted in an increase in m6A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment. CONCLUSIONS: FTO downregulation promoted UC by decreasing CerS6 expression, leading to increased S1P accumulation in IECs and aggravating colitis via m6A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment.

Recent progress on the application of compound formulas of traditional Chinese medicine in clinical trials and basic research in vivo for chronic liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic liver diseases mainly include chronic viral liver disease, metabolic liver disease, cholestatic liver disease (CLD), autoimmune liver disease, and liver fibrosis or cirrhosis. Notably, the compound formulas of traditional Chinese medicine (TCM) is effective for chronic liver diseases in clinical trials and basic research in vivo, which provide evidence of chronic liver disease treatment with integrated TCM and traditional Western medicine. AIM OF THE REVIEW: This paper aims to provide a comprehensive review of the compound formulas of TCM for treating different chronic liver diseases to elucidate the composition, main curative effects, and mechanisms of these formulas and research methods. MATERIALS AND METHODS: Different keywords related to chronic liver diseases and keywords related to the compound formulas of TCM were used to search the literature. PubMed, Scopus, Web of Science, and CNKI were searched to screen out original articles about the compound formulas of TCM related to the treatment of chronic liver diseases, mainly including clinical trials and basic in vivo research related to Chinese patent drugs, classic prescriptions, proven prescriptions, and hospital preparations. We excluded review articles, meta-analysis articles, in vitro experiments, articles about TCM monomers, articles about single-medicine extracts, and articles with incomplete or uncertain description of prescription composition. Plant names were checked with MPNS (http://mpns.kew.org). RESULTS: In this review, the clinical efficacy and mechanism of compound formulas of TCM were summarized for the treatment of chronic viral hepatitis, nonalcoholic fatty liver disease, CLD, and liver fibrosis or cirrhosis developed from these diseases and other chronic liver diseases. For each clinical trial and basic research in vivo, this review provides a detailed record of the specific composition of the compound formulas of TCM, type of clinical research, modeling method of animal experiments, grouping methods, medication administration, main efficacy, and mechanisms. CONCLUSION: The general development process of chronic liver disease can be summarized as chronic hepatitis, liver fibrosis or cirrhosis, and hepatocellular carcinoma. The compound formulas of TCM have some applications in these stages of chronic liver diseases. Owing to the continuous progress of medical technology, the benefits of the compound formulas of TCM in the treatment of chronic liver diseases are constantly changing and developing.

Intervention of Chinese Herbal Medicine Formulas on Oxidative Stress of Chronic Obstructive Pulmonary Disease： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is a common disease in clinical practice. It is associated with obvious exposure to toxic particles or gases and has become the leading cause of death and disability worldwide. The pathogenesis of COPD is complex， and the oxidative stress involved in COPD plays a crucial role in the pathological process of the disease. Patients with COPD usually have high levels of oxidative stress in the lungs， which will affect the whole body for a long time， causing a variety of complications and accelerating the development of the disease. On the one hand， oxidative stress can directly damage the airway and lung tissue. On the other hand， it also drives other pathological mechanisms to jointly promote the development of disease， such as participating in inflammatory reactions and protease/anti-protease imbalance， promoting mucus secretion， accelerating cellular senescence， causing autoimmunity， and involving in genetic regulatory pathways. At present， western medicine treatment is mostly based on conventional drug treatment， and antioxidant-targeted oxidative stress is adopted， but there are still some challenges in efficacy and safety. Traditional Chinese medicine has a long history of preventing and treating COPD. In particular， Chinese herbal medicine formulas have great potential to interfere with the oxidative stress of COPD. Whether it is the modified classical traditional Chinese medicine or the new formulation developed by modern doctors， the research results reflect the multi-target and multi-channel advantages of traditional Chinese medicine treatment， and their efficacy and safety are gradually verified. This paper reviewed the literature in recent years， starting with the basic and clinical research on the intervention of traditional Chinese herbal medicine formulas on oxidative stress of COPD， so as to provide further ideas for related research on the prevention and treatment of oxidative stress of COPD by traditional Chinese medicine.